Iodine-containing dyestuffs



Patented Jan. 6, 1942 .2,263,366 g lIODINE-CNl.ArIl\IN(,DXESTUEES l Alan v"august- Goi'aberg and rBertola frsuineinricn Wiesner, Bnadford-'on-Avon, England; assignors to Ward Blenkinsop & Company Limited, Brooklands, Halewood,'near Liverpool, England Nojpmwmg. application June jrs, 1941, serial N6. 396,668. InGreat Britain/aprilie, l1946 1o claims. (el. 26o-"1768) rIfhis invention .relates to improvements .in and relating -to iodine .containing dyestuffs. Itis already known that .certain..dyestuffs, vnotablythose .of the vChicago .'Blue and Trypan `Blue series showt-specific .aninity :for-certain tissues. We have now Afound that .this affinity .is

not impaired and that certain .pharmacologically valuable :properties areacquired'if these Adyestulfs contain iodine.

If polynuclear vdiamines such, for example, as benz'idina tolidine., .4-4 diaminodiphenylmethane, .dianisidine, 4-4' diaminostilbene'Z-Z .disul- .phonic acid, .acriflavine and derivatives thereof andthe .like are tetrazotised -and coupled with .a naphtholor aminonaphthol-monoor di-,sul- .phonic acid, dyestuis .of the Trypan Blue or Chicago .Blue `series .are produced. Inr the vcase of the Trypan vBlue fseries of .dyes the aminonaphthol monoor ,di-.sulphonate ,could be further substituted inv the orthoposition to -the .amino vgroup by .being .coupledin acid solution With .a fdiazotised .aniline, toluidine .or `like' substance .or .derivative thereof. f

Now We yhave found that one 4or ymore rof the above-mentioned components contain iodine in their molecule, they can be coupledfto form iodine-containing dyestuffs of the said types, and which will have the ainity and pharmacological properties .above-mentioned. v

ffllt'ie invention, therefore, .consists ,-inter ralia in the manufacture of iodine containing ldyestuffs by varyingthe selection of the components .from

'among the many .substances which Lean Abe cou.- pled to orm dyestuifs .of the' stated types, a 'large number of dierentsubstances coming Within 'theseop'e of the present invention canbe prepared.

'ane jin Acold aqueous solution and couplingfthis with the appropriate amino naphthol monoor di-sulphonic `acid we have been va'.'ble':1;"o prepare the k:following iodine containing dyestuius all of whichy are lofthe stated type, have strong tinc- .torial ,properties as well as 'the "other special ,properties referred to above:

"R bi-3 B-aminon'aplithol -sodium `sulphonate kwhere R l.stands for Di-iodo-diphenylmethanedisazo. -v

Similarly by replacing the di-iodo-di-amino diphenyl methane 'by di-iodo-idi-aminostilbenedi-sulphonic acid We Ahave prepared .the ycorref ,spending series of compounds in which R is replaced by R1 which standsy for Di-iodostilbene- All the above compounds are-found to be dark micro-crystalline powders which vare easily s01- uble in Water with Vthe production Aof intensely coloured solutions. Y 1' n A ,further deVelODment of vthe process accordingl to the present invention, Vwhich results in a further large number of iodine containing dyestu-ls'consists in further substituting the amino- .of the general ty-pe of Trypan Blue or Chicago naplethal-mono`` or `sdi-sulphonateV :either before or. after #the -f condensation bycoupling Ait in acid solutionv with a dazotised" iodinatedwor noniodinated arylamine such as -aniline, toluidine,

xylidine,r iodofaniline, giQdotoluidine, or iodoxylidine. LVIn this 3case=this coupling is carried out -in .aeidusolution in order that the .coupling u of the diazotised iodinatedornon-iodinated arylamine with the .aminonaphthol nucleus may take 'place in the .ortho vposition to the amino group.

vIt will, ofcourse, be understood that as it is an vobject'of `the-,invention to produce iodine containing dyestuifs yat least one of the components =.-to,.be. coupled mustcontain iodine, although more than one component mayvcontain it Vif desired; Thus. if .the diaaotised arylamine which has 'been preliminarilyv coupled with the amino naphthol itself .contains .iodine vthe polynuclear .diamine which is vtetrazotised*and used .for the final vcoupling.''mayor may not itself contain iodine. On the other 'hand if the .tetrazotised polynuclear .diamine is iodine containing,` the arylamine compound Whichis diazotised andfcoupled'with the Iamino naphthol may or vmay hot contain iodine. f

The final coupling "of the tetrazotised diamine withthe coupled :amino .naphthol 'compound is carried out in 'alkaline ysolution so'that'the Vcou- 'fllowi-ng among other compounds: l

Benzidina, rondine, '-dian1sid1ne, cli-mandiamino-diphenyl-methane, and di-iododiamlnostilbene-disulphonic acidtetrazotised and coupled with 2 mols of k1:8 amino-naphthol-Z-iodotolylazo-3z6 sodium di-sulphonate; benzidinedianisidine, tolidine and di-iododiaminodiphenylmethane-tetrazotised and coupled with 2 mols of 1:8 aminonaphthol-2-iodotolylazo-isodium sulphonate; di-iododiaminodiphenyl methane tetrazotised and coupled with 2 mols of 2 8-aminonaphthol-l-iodotolylazo-3 6 sodium disulphonate, and di-iododiaminodiphenyl methane tetrazotised and coupled'with 2mols of` 3:8- aminonaphthol 4 iodotolylazo 6 sodium sulphonate.

We have found further that it is not necessary for the purpose of the present invention that the iodine containing dyestuils should be symmetrical, but that valuable iodine containing dyestuiis, having the desired properties can readily be prepared by coupling a tetrazotised polynuclear diamine, which may or may not contain iodine, unsymmetrically with one molecule of each of two different components, which may or may not themselves contain iodine provided that atleast one of the three components be iodine-containing.

Thus, we have found that by condensing a polynuclear diamine, which may or may not be microcrystalline powder.

iodine containing, with one molecule of iodosalicyclic acid, i. e. 2-hydroxy-5-iodo-benzoic acid, and (a.) with one molecule of an aminonaphthol monoor di-sulphonic acid or (b) with one molecule of an amino naphthol-iodotolylazomonoor di-sulphonic acid by tetrazotising and,

coupling in alkaline solution dyestufs of similarly valuable properties are obtained.

In this way the following iodine containing dyestuils have been prepared: v

Diiododiaminodiphenylmethane tetrazotised and coupled with iodosalicylic acid (1 mol) and 1:8aminonaphthol-Z-iodotolylazo 3;6 sodium disulphonate (l mol).

Dianisidine tetrazotised and coupled with iodo salicylic acid (1 mol) and 1:8 aminonaphthol-Z- iodotolylazo-BrG-sodium disulphonate (1 mol).

Tolidine tetrazotised and coupled with iodo salicylic acidv(1 mol) and 1:8-aminonaphthol-2- iodotolylazo-Sz-sodium disulphonate (l mol).

Benzidine tet'razotised and coupled with iodov and they all show a selective substantivity to"- certain animal cells.

In order that our invention may be better understood, the following examples of how it may be carriedout are given only:

EXAMPLE 1 This is an example of the coupling of a tetrazotisediodinated polynuclear diamine with an aminonaphthol disulphonic acid.

4.5 parts of diiododiaminodiphenylmethane which may be prepared as described below are dissolved in 100 parts of `cold water and 25 parts acid (1 mol) and 1:8.

by Wayl of illustration of concentrated hydrochloric acid. This solution is cooled with icefand tetrazotised by -the slow.- addition of 1.4 parts of sodium nitrite dissolved in 10 parts of water. This solution is then added slowly to an ice cold solution of 7.3 parts of 1:8- aminonaphthol-326 sodium disulphonate in parts of water and 20 parts of sodium hydroxide. The mixture which rapidly assumes an intense deep purple colour is rapidly stirred for 12 hours at atmosphericr temperature and finally heated on the steam bath for a further hours during which time it is evaporated to a lesser volume. 20 parts oi sodium chloride are then added in saturated aqueous solution and then to the well cooled solution 30 parts of hydrochloric acid. After standing for several hours the diiododiphenylmethane-disazo bi-l :8-aminonaphthol-3 :6-acid sodium disulphonate is filtered off as a steel grey This is recrystallised from water and yields 9 parts of the pure dyestuff.

EXAMPLE 2 This is an example of the coupling of an aminonaphthol sodium disulphonate with a diazotised iodine containing arylamine in acid solution in order that coupling takes place ortho to the amino group in the naphthalene nucleus and coupling the resulting product in alkaline solution with a tetrazotised iodinated diamine. l,

12 parts of l-amino-2-methyl-i-iodobenzene are `converted into the hydrochloride and suspended inl v200 parts of water and 50 parts hydrochloric acid. To the rapidly agitated well cooled suspension 31A; parts of sodium nitrite are added which causes the suspension to become nearly clear. To this solution is added with rapidagi- Vtation a solution of 17 parts of H-acid in 100 parts of Water containing parts sodium carbonate. After 1 hour `a concentrated solution of 10 parts of sodium hydroxide is added and the thick brick red liquid stirred at atmospheric temperature for a further 12 hours. The liquid is then heated on the steam bath for 1 hour and the dyestuil salted out by the addition of a concentrated solution `of 20 parts sodiumchloride. The 1:8 aminonaphthol-2-iodotolylazo-3:G-hydrogen sodium disulphonate is filtered off as a deep brick red microcrystalline powder which can be recrystallised from water. l

4.5 parts of diiododiaminodiphenylmethane are dissolved and tetrazotised exactly as in Example 1 and the cold solution run into a rapidly stirred solution of 12 parts of 1:8-aminonaphthol-2- iodotolylazo-3:6-sodium disulphonate in 175 parts of water containing 20 parts of sodiumV hydroxide. After stirring for 12 hours the deep purple solution is heated on the steam bathand the dyestuff then precipitated by the addition of a saturated solution of 20 parts sodium chloride and 25 parts hydrochloric acid. After recrystallisation, the dyestuff is obtained as a steel grey powder which isy soluble in water with production of an intense purple solution. On heating the dry dyestuff on a spatula it first chars and then decomposes with evolution of clouds .of iodine vapours.

Convenient .methods .of preparing certain of the above-mentioned substances are here described.

Diiodo-diaminodphenylmethane 4:4'-diaminodiphenylmethane (20 gr.) iodine (55 gr.) calcium carbonate(40 gn), ether (50 then extracted with ethyl alcohol (ca. 1 litre) and the alcoholic extract, after filtering oi the calcium carbonate, is evaporated down to small volume and diluted with a little water. A glutinous precipitate (35 gr.) is formed which rapidly becomes friable on standing. This is separated, ground to a powder and extracted with water (250 cc.) and HC1 (50 cc.) when'the di-iodo-diaminodiphenylmethane dissolves leaving a residue (ca. 7 gr.) of tetra-iodo-diaminodiphenylmethane. The aqueous/HC1 solution of the di-iodo-diaminodiphenylmethane is treated with dilute sodium hydroxide when the free base is precipitated as a white powder which gradually darkens on standing. Yield of recrystallised material is 25 gr. (analysis gave I2=56.6%).

Di-iodo-diaminostilbenedisulpvonic acid 4 :4*-diaminostilbene-2 2'disulphonic acid (37 gr.) dissolved in water (150 cc.) andsodium hydroxide (20 gr.) is added rapidly to a solution of iodine (75 gr.) in water (150 cc.) and sodium hydroxide (30 gr.). The clear solution is heated on the steam bath overnight and in the morning cooled in ice. The heavy crystalline deposit is removed by ltration and recrystallised from the smallest amount of boiling Water when the l sodium di-iodo-diaminostilbene disulphonate (50 v ing dyestuffs by tetrazotising components consisting of polynuclear diamines and coupling them with a component of the group consisting of: a naphthol mono-sulphonic acid, a naphthol di-sulphonic acid, an arninonaphthol mono-sulphonic acid, and an aminonaphthol di-'sulphonic acid, at least one of the components containing iodine i`n the molecule.

3. A method of manufacturingiodine-containing dyestuffs as claimed in claim 2, in which the coupling component contains an amino group and is itself further substituted by being coupled in acid solution with a diazotised arylamne of the benzene series.

4. A method of manufacturing iodine-containing dyestuffs as claimed in claim 2 in which the coupling component contains an amino group and is itself further substituted by being coupled in acid solution with a diazotised arylamne of vthe benzene series containing iodine in its molecule.

5.' A method of manufacturing iodine-containing dyestuifs as claimed in claim 2 in which the coupling component contains an amino group and the resulting product is further substituted by being coupled in acid solution With a diazotised ving dyestuis as claimed in claim 2 in which the polynucelar diamine is di-iodo-di-aminostilbenev di-sulphonic acid. y

9. A method as in claim 2, wherein the tetrazotised component is also coupled with iodosalicylic acid. 1

10. A dyestui as in claim 1, wherein the tetrazotized component is also coupled with iodosalicylic acid.

ALAN AUGUST GOLDBERG. t BERTOLD PAUL HEINRICH WIESNER. 

